Diabetes Mellitus, Type 2, Pediatric

Introduction

Type 2 diabetes mellitus is a metabolic disorder characterized by peripheral insulin resistance and a failure of beta cells to compensate, leading to hyperglycemia. While once considered an adult pathology, it is increasing in prevalence in children. Risk factors for children are similar to those in adults: ethnicity, family history, obesity, and sedentary lifestyle. However, presentation and management differ from adults with the disorder. Children with diabetes (of any kind) are at an increased risk of many complications of the disease. Early recognition, screening, and treatment of children with type 2 diabetes mellitus are important for prevention of long-term complications from the disease.

Etiology

Hyperglycemia results when there is a relative lack of insulin compared to glucose in the blood. In type 2 diabetes mellitus, insulin resistance first leads to increased insulin production by the beta cells of the pancreas. When the beta cells are unable to produce enough insulin to maintain euglycemia, hyperglycemia results. Hyperglycemia has damaging effects to multiple organs, including kidneys, eyes, heart, and nerves. Further, hyperglycemia puts children at risk for other electrolyte disturbances.

Comparatively, type 1 diabetes mellitus is characterized by autoimmune destruction of beta cells in the pancreas leading to a lack of insulin production.

Epidemiology

Type 1 diabetes remains the most prevalent form of diabetes in children. However, type 2 diabetes mellitus is estimated to occur in one in three (20% to 33%) of new diagnoses of diabetes in children today. The rate of type 2 diabetes mellitus in children continues to rise even as the obesity rates have plateaued in these age groups. Risk factors include high-risk ethnicity (African American, Hispanic, Native Americans, Pacific Islanders, Asian Americans), a positive first-degree relative with the disorder, obesity, low birth weight, mother with gestational diabetes, and female sex. It is more likely to be diagnosed during adolescence when insulin resistance is common due to multiple factors including hormonal changes.

Pathophysiology

Obesity leads to peripheral insulin resistance, which in turn leads to hyperglycemia as discussed. Independent of obesity, certain ethnicities have higher risks of insulin resistance and beta cell dysfunction. Hyperglycemia leads to an osmotic diuresis (polyuria), which increases thirst (polydipsia). This diuresis causes moderate to severe dehydration. Prolonged hyperglycemia can produce two distinct emergent states in type 2 diabetes mellitus in children:

Diabetic ketoacidosis: much more common in children with type 2 diabetes mellitus compared to adults. Lack of insulin inhibits the body's ability to use glucose for energy and reverts to breaking down fat for energy. This leads to ketosis, acidosis, and electrolyte abnormalities and may lead to coma and death.

History and Physical

Children with type 2 diabetes mellitus most often present during symptomatic screening.

Children may have the typical symptoms of polyuria, polydipsia, polyphagia, and weight loss. Children with type 2 diabetes mellitus are more likely than adults with the disorder to present in DKA (5% to 13%), especially if they are of ethnic minority descent. Adolescents with type 2 diabetes mellitus may also present in Hyperosmolar Hyperglycemic State (HHS).

Physical exam findings can include acanthosis nigricans (dark, velvety rash present in the axillae and neck). The American Diabetes Association recommends screening children at 10 years old or at the start of puberty in children who are obese (> 95th percentile BMI for age) or are overweight (BMI > 85th percentile for age or > 120% ideal body weight) and have two risk factors. These factors can be positive family history, high-risk ethnicity, signs of insulin resistance (polycystic ovary syndrome (PCOS), acanthosis, symptoms), or history of maternal gestational diabetes mellitus.

Evaluation

The American Diabetes Association recommends screening for type 2 diabetes mellitus every three years starting at age ten years (or at the onset of puberty) for patients who are:

Obese (body mass index (BMI) greater than or equal to the 95th percentile for age)

Overweight (BMI greater than or equal to the 85thpercentile) and have at lease two risk factors (positive family history, higher risk race or ethnicity, signs of insulin resistance, maternal history of gestational DM).

If the diagnosis between type 1 and type 2 diabetes mellitus is not clear, helpful labs include fasting insulin or c peptide (both usually high or normal in type 2 diabetes mellitus, low in type 1 diabetes mellitus ), and autoantibodies for type 1 diabetes mellitus.

Treatment / Management

The American Academy of Pediatrics recommends lifestyle modifications and Metformin as the first line therapy. Lifestyle changes include moderate to vigorous exercise for 60 minutes per day, limiting screen time to less than two hours per day, and a dietary referral.

Metformin and/or insulin should be started at diagnosis. Metformin is first line and available as a liquid. Start at 500 mg/day and increase by 500 mg every one to two weeks to a maximum of 2000 mg twice a day. The gradual increase of the medication and taking it with food helps to prevent gastrointestinal side effects.

Insulin should be started for patients who are ketotic or in diabetic ketoacidosis (DKA), have a random blood glucose > 250 mg/dl, an A1C > 9.0%, or in whom the diagnosis of type 1 vs. type 2 is not clear. May use a basal/bolus regimen like in type 1 diabetes mellitus, but typically type 2 diabetes mellitus patients require higher doses (2 unit/kg/day - 3 unit/kg/day). Insulin should be initiated and managed by pediatric endocrinologists. Insulin takers have a risk of hypoglycemia; therefore frequent monitoring is required.

Home glucose monitoring is recommended for those who take insulin, have not met glucose control goals, are changing medications, or are sick.

A1C test goals vary by association. American Diabetes Association and the American Academy of Pediatrics list an A1C test goal of < 7%, while the American Association of Clinical Endocrinologists places the goal at < 6.5%.

Pearls and Other Issues

Complications of type 2 diabetes in children are similar to that of adults. Complications tend to occur after a person has had the disease for many years. Those who are diagnosed in childhood have the disease for longer periods of time. Therefore, strict control and management of blood glucose are crucial to help prevent these complications. All people with diabetes should have regular dilated eye exams (to examine for diabetic retinopathy), urine microalbumin screening at appropriate intervals (evaluated for renal involvement), hyperlipidemia screens/treatment, hypertension screening/treatment, and regular monitoring.